Acupuncture Treatment Extends The Cerebral Thrombolytic Time Window Associated With Regulation Of Matrix Metalloproteinases Network

Objective:To observe XNKQ acupuncture prolonged cerebral thrombolysis time window effect; XNKQ investigate protective effects of acupuncture on cerebral ischemia-reperfusion injury possible mechanism.Methods:SD rats were divided into sham operation group, model group, thrombolysis group, acupuncture+thrombolysis group (acupuncture group), the drug+thrombolysis group (control group), autologous thromboembolism method of focal cerebral ischemia rat model of blood, rt-PA thrombolysis as a means to "XNKQ" acupuncture as a means of intervention, acupuncture intervention in rats neurobehavioral science scores, the percentage of infarct volume, brain water content, cerebral hemorrhage and the permeability of the blood brain barrier; on this basis, while the use of Real-time PCR and Western blot were detected in rat cortical each group of inflammatory cytokines TNF-a, IL-1β, ICAM-1 mRNA and protein expression; and the use of gelatin zymography MMP-2, MMP-9 activity, and finally detected by Western blot using tight junction protein ZO-1, occludin expression, in order to investigate the role of acupuncture regulation of matrix metalloproteinase network mechanism.Results:1、Effect of acupuncture extended cerebral thrombolysis time window Infarction neurobehavioral scores, brain water content, cerebral hemorrhage, and blood-brain barrier permeability with the extension of thrombolysis time increased (P<0.05) in rats after thrombolytic therapy; infarct volume percentage after thrombolytic therapy and treatment no significant change compared to the previous (P>0.05); and inhibitors of acupuncture intervention could reduce neurological behavior scores, reduce infarct volume, brain water content and cerebral hemorrhage, stable blood-brain barrier permeability (P< 0.05); compared to inhibitors of acupuncture in reducing neurological behavior score, reducing the advantage on cerebral hemorrhage and stabilize blood-brain barrier permeability (P<0.05); in reducing infarct volume and brain water content two had no significant difference (P>0.05).2、Mechanism of acupuncture extended cerebral thrombolysis time window.(1) mRNA and protein expression of inflammatory factors:after thrombolytic therapy in cerebral infarction rats TNF-α, IL-1β and ICAM-1 mRNA and protein expression were significantly increased (P<0.05); and inhibitors of acupuncture interventions these three factors could reduce inflammatory mRNA and protein expression (P<0.05); compared to inhibitors of acupuncture in reducing advantage on ICAM-1 mRNA and protein expression (P<0.05); and in reducing TNF-a, no significant difference (P>0.05) on the mRNA and protein expression of both IL-1β.(2) Matrix metalloproteinase activity:Comparison of MMP-2 and MMP-9 before and after thrombolysis difference was statistically significant (P<0.05); MMP-9 activity after acupuncture and inhibitors can reduce the thrombolysis and acupuncture effect is greater than inhibitor effect (P<0.05); and acupuncture in reducing MMP-2 inhibitors and thrombolysis group difference was not statistically significant (P>0.05)(3) Tight junction protein expression:cerebral infarction after thrombolytic therapy occludin and ZO-1 protein expression in rats with the extension of thrombolysis decreased (P<0.05); Acupuncture and inhibitors can improve cerebral thrombolysis protein expression in rat occludin and ZO-l’s (P<0.05); compared inhibitors, acupuncture improve thrombolysis in cerebral infarction rats occludin and ZO-1 protein expression is more significant (P<0.05).Conclusion:Cerebral ischemia Thrombolysis strictly limited time window, over a time window of thrombolysis can cause neurological damage and blood brain barrier and hemorrhagic transformation, and these effects with prolonged thrombolytic time and aggravation. XNKQ acupuncture and a broad spectrum of MMPs inhibitor doxycycline can be improved by cerebral ischemia reperfusion injury in rats with nerve function, reduce blood-brain barrier permeability changes after thrombolysis, and hemorrhagic transformation to achieve prolonged brain infarction time window effect, and the former than the latter neuroprotective effect is more obvious. In addition, XNKQ acupuncture compared with a broad spectrum of MMPs inhibitor doxycycline can be more significant inhibition of cerebral ischemia and reperfusion mRNA and protein expression in rat cortex correlated cytokines, which in turn inhibits MMP-2, MMP-9 over activated to regulate the expression of tight junction proteins, regulation of MMPs from the network approach to better protect the brain tissue.